1st July 2021
FOI 21/611
Dear
REG 174 for Pfizer COVID-19 mRNA Vaccine BNT162b2 to be corrected
Thank you for your information request, dated 02 June 2021, where you asked the following:
In REG 174 for Pfizer COVID-19 mRNA Vaccine BNT162b2; under 5.2 Pharmacokinetic properties it states “Not Applicable”.
Herewith does MHRA suggest that the novel mRNA COVID vaccines behave like “traditional” vaccines and the vaccine spike protein — responsible for infection and its most severe symptoms — would remain mostly in the vaccination site at the shoulder muscle.
However, there is a Pharmacokinetic property study done “2.6.5B Pharmacokinetics: Organ distribution. Test Article Labelled LNP mRNA formulation containing ALC-0315 and ALC 0159. Report number 185350” see https://urldefense.proofpoint.com/v2/url?u=https-3A__www.docdroid.net_xq0Z8B0_pfizer-2Dreport-2Djapanese-2Dgovernment-2Dpdf&d=DwIFaQ&c=bXyEFqpHx20PVepeYtwgeyo6Hxa8iNFcGZACCQj1uNM&r=km_DIOctokEVZj2AvNHi6w&m=KgCVbIdZgoqu6itMZEMWjge9kMiHaZrw3NnJCExSuXs&s=9qKrT2vQD3LD0hTlvoyjpc1xApf5U3rRfgwmm9qExIk&e=
This Japanese data shows that the spike protein of the Pfizer ‘vaccine’ gets into the blood where it circulates for several days post-vaccination and then accumulated in organs and tissues including the spleen, bone marrow, the liver, adrenal glands, and in the ovaries.
Once in circulation, the spike protein can attach to specific ACE2 receptors that are on blood platelets and the cells that line blood vessels. This can either cause platelets to clump, and that can lead to clotting. It can also lead to bleeding.
This study looked at the vaccine distribution (as of ALC 0315/0159 plasma level) in about 45 organs were measured over time intervals of 15 min, 1hr, 2hr, 4hr, 8hr, 24hr and 48 hr. Pharmacokinetic studies have also been done over the days up to a 9 days period.
The study shows that in many organs the vaccine plasma level keeps rising after 2 days (concentration (ug lipid equivalent/g [or mL]: males and females combined) (ranking) Liver (24.3); Spleen (23.4); Adrenaline glands (18.2); Ovarium (12.3); Bone marrow (3,77); Pancreas (0.6); Uterus (0.5); Testes (0.3); Eyes (0.1) To note is that the Adrenaline glands being affected by high plasma levels will cause an overall organ stress; which in turn affects particular the immune and the nervous system.
Compare that to Pfizer vaccine’s Adverse Drug Reaction (see yellow cards of 21 May) in related organs (ranking in % of vaccine doses): Nervous system disorders 0.14%; Muscle & tissue disorders 0.1%; Gastrointestinal disorders 0.08%; Skin disorders 0.06%; Respiratory disorders 0.035%; Eye disorders 0.012%; Blood disorders 0.026%; Infections 0.02%; Cardiac disorder 0.01%; Reproductive & breast disorder 0.0116%
Further it is shown that the COVID-19 mRNA Vaccine BNT162b2 is excreted in human milk: babies got Thrombotic Thrombocytopenic Purpura and died.
Moreover, there is a coloration between the Pharmacokinetics and the vaccine injuries.
Therefor significant changes have to be made in Reg 174 or better due to the seriousness of the found injuries; it should be withdrawn.
Question: In case MHRA does (according to the above findings) not amend or withdrawn its current version: please state why and which study supports such reasoning
You also commented.
Please do integrate in our Ref: FOI 21/611 the following information:
European Medicines Agency (EMA) reviewers revealed Pfizer didn’t thoroughly examine biodistribution and pharmacokinetics issues relating to its vaccine before submitting the vaccine to the EMA. Its reviewers shared with the HMRA this explicit admission: “No traditional pharmacokinetic or biodistribution studies have been performed with the vaccine candidate BNT162b2.”
In fact, in key studies — called biodistribution studies, which are designed to test where an injected compound moves throughout the body — the time course of its absorption, bioavailability, distribution, metabolism and excretion travels in the body, and which tissues or organs it accumulates in — Pfizer did not use the commercial vaccine (BNT162b2) but instead relied on a “surrogate” mRNA that produced the luciferase protein.
Regulatory documents also show Pfizer did not follow industry-standard quality management practices during preclinical toxicology studies of its vaccine, as key studies did not meet good laboratory practice (GLP). GLPs, are of paramount importance for quality and ultimately for patient safety. If such important steps are skipped, the risk-benefit analysis would need to be compelling.”
Additionally, the EMA document states, “Biodistribution: Several literature reports indicate that LNP-formulated RNAs can distribute rather non-specifically to several organs such as spleen, heart, kidney, lung and brain. In line with this, results from the newly transmitted study 185350 indicate a broader biodistribution pattern.” This EMA observation corresponds with a growing number of adverse events and aligns with data TrialSite obtained through FOIA showing concentrations of LNP-formulated RNAs in the spleen, ovaries, other tissues and organs.
A quick review the Toxicology Section (2.3.3) of the EMA Assessment Report on Comirnaty (BNT162b2) issued on 19 Feb. 2021, raises concerns about data applicability of preclinical study findings to clinical use: “To determine the biodistribution of the LNP-formulated modified mRNA (modRNA), the applicant did study distribution of the modRNA in two different non-GLP studies, in mice and rats, and determined the biodistribution of a surrogate luciferase modRNA. Thus, one might question the validity and applicability of non-GLP studies conducted using a variant of the subject mRNA vaccine. “In addition, no genotoxicity data were provided to EMA [& to MHRA].”
Pre-clinical studies showing BNT162b2’s active part (mRNA-lipid nanoparticles) — which produce the spike protein — did not stay at the injection site and surrounding lymphoid tissue as scientists originally theorized, but spread widely throughout the body and accumulated in various organs, including the ovaries and spleen. Research suggests this could lead to the production of spike protein in unintended places, including the brain, ovaries and spleen, which may cause the immune system to attack organs and tissues resulting in damage, and raises serious questions about genotoxicity and reproductive toxicity risks associated with the vaccine.
Whilst MHRA REG 174 (on BNT162b2) states that the studies performed and submitted by Pfizer all fulfilled the GLP standards: they were actually non-GLP. Moreover, MHRA provided Pfizer an exception to this GLP regulatory rule: despite that BNT162b is based on a radically new life science-based technology, and that Pfizer having been fined several times for being dishonest in the data they supplied.
Now that the MHRA is explicitly informed about Pfizer having withheld, forged and frauded essential GLP data concerning its vaccine biodistribution and pharmacokinetics; MHRA’ conclusion that BNT162b is safe is false. The MHRA should interpretate that its Adverse Drug Reaction results on its yellow card report to be related to BNT162b2’ biodistribution and pharmacokinetics.
Whereas Pfizer’s vaccine BNT162b’s risk-benefit analysis is negative; therefor should BNT162b’ Emergency Use Authorization approval be withdrawn.
Yet if the MHRA does not do make such interpretation and withdraw: then what are MHRA’ reasons
Please see below our responses to your question.
Distribution of the vaccine
The first part of your enquiry concerns the distribution of the Pfizer/BioNTech COVID-19 vaccine. Pharmacokinetic (PK) studies are generally not considered necessary to support the development and licensing of vaccine products for infectious diseases (WHO guidelines on nonclinical evaluation of vaccines, 2005). However, specific studies can be considered on a case by case basis. For the Pfizer/BioNTech COVID-19 vaccine the adsorption, distribution, metabolism, excretion (ADME) profile of BNT162b2 included an evaluation of the pharmacokinetics and metabolism of two lipid excipients (ALC-0315 and ALC-0159) and the potential in vivo biodistribution of the vaccine using luciferase RNA expression as a surrogate reporter.
The downloaded report from the link you provided appears to be from the common technical document (CTD) presumably submitted to Japan’s Pharmaceuticals and Medical Devices Agency. The document is in Japanese and has not been evaluated but based on the tables/figures in the document it appears to be an amalgamation of different reports the MHRA and the European Medicines Agency (EMA) have previously reviewed. These studies are summarised in the MHRA and EMA public assessment reports which provide the basis for approval of the vaccine. Links to these are provided below:
https://www.gov.uk/government/publications/regulatory-approval-of-pfizer-biontech-vaccine-for-covid-19
https://www.ema.europa.eu/en/documents/assessment-report/comirnaty-epar-public-assessment-report_en.pdf
The study you highlight in your question is a tissue distribution study using a [3H]-labelled lipid nanoparticle-mRNA formulation containing the lipids ALC-0315 and ALC-0159 following intramuscular administration in rats. In this study the greatest concentration of radioactivity was found remaining in the injection site at each time point, with low levels of radioactivity detected in most tissues. It should be noted that the distribution of the lipid nanoparticles was measured using a radioactive label (tritium) in a lipid component. The data do not allow a judgment on the distribution of the mRNA component or expression and distribution of the encoded COVID-19 spike protein. Whilst the lipid was widely distributed, the amounts outside the injection site and liver were small and were not associated with any adverse effects. In the repeated dose preclinical toxicity studies, no adverse effects outside of the expected inflammation associated with an immune response were detected.
Safety of breast-feeding
In your letter you suggest “that the COVID-19 mRNA Vaccine BNT162b2 is excreted in human milk: babies got Thrombotic Thrombocytopenic Purpura and died”. We are not aware from UK Yellow Card data of any similar reports with breastfed infants. We are also not currently aware of any evidence that the COVID-19 mRNA Vaccine BNT162b2 or other approved COVID vaccines are transferred to human breast milk. Recent published data suggest that mRNA from COVID-19 BNT162b2 (Pfizer) and mRNA-1273 (Moderna) vaccines are not detected in human breast milk samples collected 4-48 hours post-vaccination(Golan et al 2021 https://www.medrxiv.org/content/10.1101/2021.03.05.21252998v1).
The current Joint Committee on Vaccination and Immunisation (JCVI) advice is that women who are breastfeeding can be given the COVID-19 mRNA Vaccine BNT162b2 (this advice is also in line with breastfeeding advice for the COVID-19 AstraZeneca vaccine).
Adverse event profile of the vaccine
The Pfizer/BioNTech vaccine was evaluated in clinical trials involving more than 44,000 participants. The most frequent adverse reactions in trials were pain at the injection site, fatigue, headache, myalgia (muscle pains), chills, arthralgia (joint pains), and fever; these were each reported in more than 1 in 10 people. These reactions were usually mild or moderate in intensity and resolved within a few days after vaccination. The MHRA continually monitors the safety of COVID-19 vaccines available in the UK. A weekly summary of Yellow Card reporting is published by the MHRA. These reports can be found at https://www.gov.uk/government/publications/coronavirus-covid-19-vaccine-adverse-reactions/coronavirus-vaccine-summary-of-yellow-card-reporting
Question: In case MHRA does (according to the above findings) not amend or withdrawn its current version: please state why and which study supports such reasoning
As of 16 June, an estimated 16.8 million first doses of the Pfizer/BioNTech vaccine and around 10.9 million second doses have been administered. As of 16 June 2021, for the UK, 73,944 Yellow Cards have been reported for the Pfizer/BioNTech vaccine. For all COVID-19 vaccines, the overwhelming majority of reports relate to injection-site reactions (sore arm for example) and generalised symptoms such as ‘flu-like’ illness, headache, chills, fatigue (tiredness), nausea (feeling sick), fever, dizziness, weakness, aching muscles, and rapid heartbeat. Generally, these happen shortly after the vaccination and are not associated with more serious or lasting illness. In clinical trials, the Pfizer/BioNTech vaccine has demonstrated very high levels of protection against symptomatic infection. Data is now available on the impact of the vaccination campaign in reducing infections and illness in the UK (https://www.gov.uk/government/publications/phe-monitoring-of-the-effectiveness-of-covid-19-vaccination ). All vaccines and medicines have some side effects. These side effects need to be continuously balanced against the expected benefits in preventing illness. As with all vaccines and medicines, the safety of COVID-19 vaccines is continuously monitored and benefits and possible risks remain under review.
Thank you for your inquiry and please contact us should you have further questions.
Yours sincerely
FOI Team,
Vigilance and Risk Management of Medicines Division
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